P,P-Diphenylphosphinic azide → HCID 14942555, compound

HRID 2287823Notes

Reaction equation

HRID 2287823 reaction equation
[NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C:8]([NH:10][CH2:11][C:12]([NH:14][C@@H:15]([C:17]([NH:19][CH2:20][C:21]([OH:23])=O)=[O:18])[CH3:16])=[O:13])=[O:9])[CH3:7])=[O:4].Cl.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>CN(C=O)C.O>[NH:1]1[C:21](=[O:23])[CH2:20][NH:19][C:17](=[O:18])[C@@H:15]([CH3:16])[NH:14][C:12](=[O:13])[CH2:11][NH:10][C:8](=[O:9])[C@H:6]([CH3:7])[NH:5][C:3](=[O:4])[CH2:2]1

Participants

5

Reactant 2

HCID 199401P,P-Diphenylphosphinic azideHCID 131719923HCID 131719923, compound

Product 1

HCID 14942555HCID 14942555, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
-40 °C

Procedure

This compound was synthesized by the method of Veber, D. F. et al, J. Org. Chem. 44, 3101-5 (1979). To a solution of Gly-Ala-Gly-DAla-Gly.HCl prepared as in Example 34D (9.70 g, 26.4 mmol) in anhydrous DMF (3200 ml) was added enough TEA to adjust the pH to ~8 (measured by spotting the reaction mixture on moistened Hydrion paper) and the resulting mixture was cooled to -40° C. To this mixture was added DPPA (8.86 g, 32.2 mmol) dropwise over 5 min. The temperature was maintained at ~-35° C. for a period of 5 h and then the reaction mixture was stored at -25° C. (internal temperature) for 48 h thereafter. During this time the pH was monitored periodically (as described above) and maintained at ~8 by the addition of TEA. After this time the reaction mixture was allowed to stand at 0° C. for 48 h. Again the pH was monitored periodically and maintained at ~8 by the addition of TEA. After this time the reaction was diluted with water (3200ml) and stirred with Bio-Rad AG 501-X8 (mixed-bed) resin (1500 g) for 6 h. The resin was separated by filtration and the solution was concentrated to dryness. Trituration of the residue with refluxing THF for 12 h, filtration of the hot THF and drying at high vacuum afforded 5.50 g (67% yield) of the product as a white powder: mp >300° C. (dec); 1H NMR (DMSO-d6) δ 1.16-1.25 (m, 6 H), 3.38-4.23 (m, 8 H), 7.55 (t, J=5.6 Hz, 1 H), 7.60 (t, J=5.4 Hz, 1 H), 8.20-8.25 (m, 1 H), 8.40 (d, J=7.6 Hz, 1 H); FAB mass spectrum (NBA+Li+) m/z 320 (M+Li)+.

Workup

  1. customThis compound was synthesized by the method of Veber, D
  2. additionwas added enough TEA
  3. temperatureThe temperature was maintained at ~-35° C. for a period of 5 h
  4. customwas stored at -25° C.
  5. customfor 48 h
  6. temperaturemaintained at ~8 by the addition of TEA
  7. temperaturemaintained at ~8 by the addition of TEA
  8. customThe resin was separated by filtration
  9. concentrationthe solution was concentrated to dryness
  10. waitTrituration of the residue with refluxing THF for 12 h
  11. filtrationfiltration of the hot THF
  12. customdrying at high vacuum

Sources & evidence

ORD record
ord-b0bbad1d9ded4caeabe37ae087b16d11
Source dataset
uspto-grants-2000_07
Patent number
US06084093

Reaction notes

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